The FDA’s Quality Revolution

By Peter J. Pitts

Let it be said that the spark that ignited the flame was when FDA leadership asked, “Do we know enough about the quality of drugs that are sold in the United States.”

So said, CDER Director Dr. Janet Woodcock during yesterday’s webinar, “Understanding CDER’s “Super” Office Of Pharmaceutical Quality and Its Effect on You.”  Dr. Woodcock was joined by Dr. Lawrence Yu. I was honored to moderate the FDA News-sponsored session.

(Janet is the acting director of the OPQ and Lawrence is the acting deputy.)

Let’s put the new OPQ into some historical context.

In 2009, the FDA announced its Safe Use of Drugs Initiative.  The theory being that one way to make drugs safer is to ensure that they are used as directed. The main strategy was education and the agency’s efforts were (and are) aimed at physicians, nurses, pharmacists, and patients.

Earlier this year, the agency announced not just an office, but a Super Office of Pharmaceutical Quality, further underscoring that the FDA operates not under a two-dimensional system of safety and efficacy, but a three-dimensional approach that includes quality … with a capital (indeed a “super”) Q.

Since there is no such thing as a safe substandard product, the agency is putting time, resources, and the use of the bully pulpit to go beyond cGMPs, API and excipient sourcing to develop a risk-based approach that includes data gathered from a variety of sources including manufacturing inspections, adverse event reporting, and substandard pharmaceutical events as evidenced in the agency’s bioequivalence- driven actions with bupropion in 2012, metoprolol in 2014, and methylphenidate in 2015.

So, in many respects, pharmaceutical quality is both a pre and post-licensure endeavor and, like Safe Use, a scientific and educational enterprise that requires close coordination with many stakeholders. And it won’t come easily or inexpensively.

Aristotle said that, “Quality is not an act, it is a habit.”

I began the interview by asking Dr. Woodcock, “how is the FDA going to make pharmaceutical quality a habit?” She responded by sharing her belief that industry must “own” quality – and must be able to measure it. As the saying goes, that which gets measured gets done.

The OPQ philosophy is more than just about NDA/ANDA parity. It’s not just a “promotion” for quality – it’s a quality revolution that goes from top to bottom. But, as Audre Lorde reminds us, “Revolution is not a onetime event.” This adage should be inscribed on the wall at OPQ.

Dr. Woodcock stressed the need for the FDA to treat the issue of quality from a much more senior-level perspective. The immediate result will be the creation of a separate policy function for quality issues within OPQ.

(She was wisely noncommittal on whether or not the agency would be requesting additional funding for OPQ via PDUFA VI.)

One of the pillars of quality, of course, is inspection. Dr. Yu made it clear that, in the new OPQ era, the FDA would be going “beyond documentation.” In other words (to borrow a phrase from the arms control lexicon), “trust but verify.”

An immediate result is a new paradigm for inspections and reports that will advance pharmaceutical quality. The new standardized approach to inspection will include:

  • Data gathering to inform “quality intelligence” of sites and products
  • Risk-based and rule-based process, using expert questions
  • Semi-quantitative scoring to allow for comparisons within and between sites
  • More common inspection report structure
  • Positive behaviors recognized and rewarded where facilities exceed basic compliance

OPQ is, as both Janet and Lawrence said, about having the agency speak with “One Quality Voice.” Specifically:

Put patients first by balancing risk and availability

  • Ensure clinically relevant quality standards
  • Integrate review and inspection across product lifecycle
  • Maximize efficiency by applying risk-based approaches
  • Strengthen lifecycle management by using team-based processes
  • Effectively apply staff expertise to enhance quality regulation
  • Encourage innovation by advancing new technology and manufacturing science
  • Enhance cross-disciplinary interaction, shared accountability, and joint problem solving
  • Build collaborative relationships by communicating openly, honestly, and directly

And the major foundation is product quality informatics. In the “knowledge is power” category OPQ recognizes that enabling an efficient science-driven assessment requires significant transformation in how they collect, evaluate, and learn from the product quality data. Specifically:

  • Core areas of Product Quality Informatics: Structured data submission and collection
  • Knowledge management and communication Established conditions
  • Risk mitigation
  • Post-market surveillance and quality monitoring
  • Intelligent data analysis

Both Janet and Lawrence underscored the importance of cross-office cooperation  (via “program alignment agreements”) and specifically mentioned working with the Office of Surveillance and Epidemiology to better understand how pharmacovigilance signals can inform the agency’s actions on quality problems.

Drs. Woodcock and Yu also spoke to the urgency of a more regular and risk-based approach to changes in API and excipient sourcing, as well as more systematic monitoring of bioequivalence. Both she and Dr. Yu agreed that the agency’s new respect for quality would influence their views on both the review and post-marketing surveillance of both biosimilars and non-biologic complex drugs (NBCDs).

Make no mistake — the Office of Pharmaceutical Quality is a regulatory revolution. And Drs. Woodcock and Yu are regulatory revolutionaries. And (as Abbie Hoffman quipped), “the first duty of a revolutionary is to get away with it.

Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest.

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One Response to The FDA’s Quality Revolution

  1. Tracy Chen says:

    You have really captured the essence of quality and the latest OPQ vision on quality in your article. I have found it to be extremely insightful! Thank you!

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